Common variants conferring risk of schizophrenia.
Common variants conferring risk of schizophrenia.
复制标题
DOI：
10.1038/nature08186
复制
发表时间：
2009-08-06
期刊：
影响因子：
64.8
通讯作者：
Collier, David A.
中科院分区：
文献类型：
--
作者：
Stefansson, Hreinn;Ophoff, Roel A.;Steinberg, Stacy;Andreassen, Ole A.;Cichon, Sven;Rujescu, Dan;Werge, Thomas;Pietilainen, Olli P. H.;Mors, Ole;Mortensen, Preben B.;Sigurdsson, Engilbert;Gustafsson, Omar;Nyegaard, Mette;Tuulio-Henriksson, Annamari;Ingason, Andres;Hansen, Thomas;Suvisaari, Jaana;Lonnqvist, Jouko;Paunio, Tiina;Borglum, Anders D.;Hartmann, Annette;Fink-Jensen, Anders;Nordentoft, Merete;Hougaard, David;Norgaard-Pedersen, Bent;Bottcher, Yvonne;Olesen, Jes;Breuer, Rene;Moeller, Hans-Jurgen;Giegling, Ina;Rasmussen, Henrik B.;Timm, Sally;Mattheisen, Manuel;Bitter, Istvan;Rethelyi, Janos M.;Magnusdottir, Brynja B.;Sigmundsson, Thordur;Olason, Pall;Mason, Gisli;Gulcher, Jeffrey R.;Haraldsson, Magnus;Fossdal, Ragnheidur;Thorgeirsson, Thorgeir E.;Thorsteinsdottir, Unnur;Ruggeri, Mirella;Tosato, Sarah;Franke, Barbara;Strengman, Eric;Kiemeney, Lambertus A.;Melle, Ingrid;Djurovic, Srdjan;Abramova, Lilia;Kaleda, Vasily;Sanjuan, Julio;de Frutos, Rosa;Bramon, Elvira;Vassos, Evangelos;Fraser, Gillian;Ettinger, Ulrich;Picchioni, Marco;Walker, Nicholas;Toulopoulou, Timi;Need, Anna C.;Ge, Dongliang;Yoon, Joeng Lim;Shianna, Kevin V.;Freimer, Nelson B.;Cantor, Rita M.;Murray, Robin;Kong, Augustine;Golimbet, Vera;Carracedo, Angel;Arango, Celso;Costas, Javier;Joensson, Erik G.;Terenius, Lars;Agartz, Ingrid;Petursson, Hannes;Nothen, Markus M.;Rietschel, Marcella;Matthews, Paul M.;Muglia, Pierandrea;Peltonen, Leena;St Clair, David;Goldstein, David B.;Stefansson, Kari;Collier, David A.
精神分裂症是一种复杂的疾病，由遗传和环境因素及其相互作用引起。对发病机制的研究传统上集中在大脑中的神经递质系统，特别是那些涉及多巴胺的系统。一个多世纪以来，精神分裂症一直被认为是一种单独的疾病，但在缺乏明确的生物标志的情况下，历史上一直是根据体征和症状进行诊断。从与疾病相关的拷贝数变异(CNV)的全基因组关联研究中出现的一个基本信息是，其遗传基础不一定符合经典的病因学疾病边界。某些CNV不仅具有较高的精神分裂症相对风险，而且还具有其他精神疾病的相对风险。与精神分裂症相关的结构变异可能涉及几个基因，表型综合征或“基因组障碍”尚未得到表征。基于单核苷酸多态性(SNP)的全基因组关联研究可能会揭示复杂疾病中单个基因的潜在生物学途径。在这里，我们结合了来自几个大型全基因组扫描的SNP数据，并跟踪了最重要的关联信号。我们发现与位于染色体6p21.3-22.1上的主要组织相容性复合体(MHC)区域的几个标记、位于11q24.2上的神经颗粒素基因(NRGN)上游的一个标记以及位于18q21.2上的转录因子4(TCF4)内含子的一个标记显著相关。我们的发现表明，MHC区域与精神分裂症风险的免疫成分是一致的，而与NRGN和TCF4的关联则指向参与大脑发育、记忆和认知的通路的扰动。
Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the ‘genomic disorders’, have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
登录
查看更多内容
影响因子：
64.8
作者：
Stone, Jennifer L.;O'Donovan, Michael C.;Gurling, Hugh;Kirov, George K.;Blackwood, Douglas H. R.;Corvin, Aiden;Craddock, Nick J.;Gill, Michael;Hultman, Christina M.;Lichtenstein, Paul;McQuillin, Andrew;Pato, Carlos N.;Ruderfer, Douglas M.;Owen, Michael J.;St Clair, David;Sullivan, Patrick F.;Sklar, Pamela;Purcell, Shaun M.;Scolnick, E. M.;Holmans, P. A.;Georgieva, L.;Nikolov, I.;Norton, N.;Williams, H.;Williams, N. M.;Toncheva, D.;Milanova, V.;Thelander, E. F.;Morris, D. W.;O'Dushlaine, C. T.;Kenny, E.;Waddington, J. L.;Choudhury, K.;Datta, S.;Pimm, J.;Thirumalai, S.;Puri, V.;Krasucki, R.;Lawrence, J.;Quested, D.;Bass, N.;Curtis, D.;Crombie, C.;Fraser, G.;Kwan, S. L.;Muir, W. J.;McGhee, K. A.;Pickard, B.;Malloy, P.;Maclean, A. W.;Van Beck, M.;Visscher, P. M.;Macgregor, S.;Pato, M. T.;Medeiros, H.;Middleton, F.;Carvalho, C.;Morley, C.;Fanous, A.;Conti, D.;Knowles, J. A.;Ferreira, C. P.;Azevedo, M. H.;McCarroll, S. A.;Gates, C.;Daly, M. J.;Sklar, P.
通讯作者：
Sklar, P.
影响因子：
17.7
作者：
Eaton, WW;Byrne, M;Mortensen, PB
通讯作者：
Mortensen, PB
影响因子：
4.8
作者：
Ruano, Dina;Aulchenko, Yuril S.;Palha, Joana A.
通讯作者：
Palha, Joana A.
影响因子：
30.8
作者：
Kong A;Masson G;Frigge ML;Gylfason A;Zusmanovich P;Thorleifsson G;Olason PI;Ingason A;Steinberg S;Rafnar T;Sulem P;Mouy M;Jonsson F;Thorsteinsdottir U;Gudbjartsson DF;Stefansson H;Stefansson K
通讯作者：
Stefansson K
DOI：
10.1073/pnas.0707456104
发表时间：
2007-09-25
影响因子：
11.1
作者：
Flora, Adriano;Garcia, Jesus J.;Zoghbi, Huda Y.
通讯作者：
Zoghbi, Huda Y.